The routine administration of therapeutic proteins and peptides is hindered by the lack of a reliable and convenient mode of delivery. The oral route is often impractical due to the digestion of proteins in the gastrointestinal tract. Parenteral administration is an alternative, although frequent injections are required due to the short half-life of peptides and this can decrease patient compliance.
Other potential routes of administration for proteins include nasal, pulmonary, rectal, vaginal, ocular and transdermal. The transdermal route offers some advantages in that the skin has low proteolytic activity, so that metabolism of the protein during transit through the skin is minimized thereby improving bioavailability.
One problem with transdermal administration of proteins and peptides is that they may exhibit very low permeability through the skin due to their hydrophilicity and high molecular weight. One approach to overcoming the low skin permeability is directed to temporarily compromising the integrity or physicochemical characteristics of the skin to enhance skin penetration, e.g., using a skin penetration enhancer, employing ultrasonic vibration, removing the epithelial layer by suction or employing an electric current (iontophoresis). These approaches have demonstrated the feasibility of transdermal administration of proteins and peptides, however are associated with skin irritation and/or other disadvantages.